We have developed several lines of evidence in support of the position that the neurotransmitters (acetylcholine, dopamine) and the neuromodulator serotonin are coupled together critically in the caudate nucleus to comprise a neurochemical system for regulating involuntary movements. Thus, we demonstrated that during periods of increased functional cholinergic activity (inhibition of local cholinesterase; or interference with caudate dopamine) resulting in tremors, there is an increased compensatory turnover of dopamine (potentiated by MAO inhibitors, e.g., pargyline). The functioning of this neurotransmitter system is dependent on the levels of ionized Ca ions (chelation of Ca ions results in involuntary movements) and is modulated by serotonin (higher levels enhance excitatory action of acetylcholine); the monoamine oxidase level of activity thus plays a critical role. A microinjection- electrical recording technique ("injectrode") has been used to analyze the effects of several psychoactive drugs (MAO inhibitors, amphetamine, morphine) on these established local neuroregulator mechanisms, utilizing involuntary movement responses and brain electrical activity as sensitive indices of changes in caudate functioning. Along related lines, we plan to extend our investigations of direct and indirect effects of these and other psychotropic drugs on hippocampal excitability as reflected by changes in repetitive discharge patterns (chemically-induced and standardized) in the hippocampus and other neurophysiologically-related brain areas. For example, an analysis of these changes has provided us with a basis for explaining the biphasic affects of hydromorphone in the hippocampus: low doses of hydromorphone depressed local acetylcholine activity (lower DFP discharges) to decrease hippocampal excitability; whereas, higher doses, increased hippocampal excitability and were focogenic. In both the caudate nucleus and hippocampus the actions of the psychotropic drugs will be interpreted primarily with regard to their influence on local neurotransmitter mechanisms.